The present invention relates to a process for producing oxadiazoline derivatives (for example, compounds [IX], [IXa] and the like described hereinafter), intermediates for synthesis of the oxadiazoline derivatives, and a process for producing the intermediates. The oxadiazoline derivatives are useful as insecticides and acaricides.
So far, known processes for producing xcex942-1,2,4-oxadiazoline derivatives having a pyrazol substituent at the 3-position thereof include e.g. a process for producing the derivatives from cyanopyrazol derivatives (JP-A 10-152476).
However, a process for synthesizing 3-pyrazolyl-xcex942-1,2,4-oxadiazoline derivatives having various kinds of substituents on the nitrogen atom at the 4-position of the oxadiazoline ring is still not known, and at present, there is no satisfactory process as a general or industrial process for synthesis of xcex942-1,2,4-oxadiazoline derivatives useful as insecticides and acaricides.
An object of the present invention is to provide a satisfactory process as a general or industrial process for synthesizing xcex942-1,2,4-oxadiazoline derivatives useful as insecticides and acaricides.
The present inventors extensively studied for solving the problem described above, and unexpectedly found that 3-pyrazolyl-xcex942-1,2,4-oxadiazoline derivatives can be synthesized in high yield by the ring transformation reaction of 3-isoxazolyl-xcex942-1,2,4-oxadiazoline derivatives, and the present invention was thereby completed.
That is, the present invention relates to:
1. A process for producing isoxazole-5-carboxamide oxime represented by formula [I]: 
or a salt thereof, which comprises reacting 5-cyanoisoxazole with hydroxylamine or a salt thereof;
2. A process for producing 3-(5-isoxazolyl)-xcex942-1,2,4-oxadiazoline represented by formula [II]: 
or a salt thereof, which comprises reacting isoxazole-5-carboxamide oxime represented by formula [I]: 
or a salt thereof with formaldehyde or an equivalent thereof;
3. A process for producing a compound represented by formula [IV]: 
wherein R1 represents an optionally substituted alkyl group, an optionally substituted acyl group or chlorocarbonyl group (ClCO), or a salt thereof, which comprises reacting 3-(5-isoxazolyl)-xcex942-1,2,4-oxadiazoline represented by formula [II]: 
or a salt thereof with a compound represented by formula [III]:
R1X1xe2x80x83xe2x80x83[III]
wherein X1 represents a halogen atom, and R1 is as defined above, or an equivalent thereof or a salt thereof;
4. A process for producing a compound represented by formula [V]: 
wherein R1 is as defined in the above 3, or a salt thereof, which comprises subjecting a compound represented by formula [IV]: 
wherein R1 is as defined in the above item 3, or a salt thereof to the ring-opening reaction of the isoxazole ring;
5. A process for producing a compound represented by formula [VII]: 
wherein R1 is as defined in the above item 3, and R2 represents (1) halogen, (2) C1-6 haloalkyl group, (3) C1-6 haloalkoxy group or (4) phenyl group optionally substituted with a C1-6 haloalkyl group] or a salt thereof, which comprises reacting a compound represented by formula [V]: 
wherein R1 is as defined in the above item 3, or a salt thereof with a compound represented by formula [VI]: 
wherein A represents a nitrogen atom or 
(wherein R3 represents chlorine atom or cyano group, and the other symbol is as defined above, or a salt thereof;
6. A process for producing a compound represented by formula [IX]: 
wherein R1 is as defined in the above item 3, R2 and A are as defined in the above item 5, and R4 represents a C1-6 alkyl group or C1-6 haloalkyl group, or a salt thereof, which comprises reacting a compound represented by formula [VII]: 
wherein R1 is as defined in the above item 3, and R2 and A are as defined in the above item 5, or a salt thereof with a compound represented by the formula [VIII]:
R4SOnX2xe2x80x83xe2x80x83[VIII]
wherein R4 is as defined above, n is 0, 1 or 2, and X2 represents a halogen atom;
7. A process for producing a compound represented by formula [IVb]: 
wherein R5 and R6 each represent a C1-6 alkyl group, or R5 and R6, together with their adjacent nitrogen atom, represent a cyclic amino group, or a salt thereof, which comprises reacting a compound represented by formula [IVa]: 
wherein X represents a chlorine atom, 1-chloroethoxy group, chloromethoxy group or phenoxy group, or a salt thereof with an amine represented by formula [X]:
R5R6NHxe2x80x83xe2x80x83[X]
wherein the symbols are as defined above, or a salt thereof;
8. A process for producing a compound represented by formula [Va]: 
wherein R5 and R6 are as defined in the above item 7, or a salt thereof, which comprises subjecting a compound represented by formula [IVb]: 
wherein R5 and R6 are as defined in the above item 7, or a salt thereof to the ring-opening reaction of the isoxazole ring;
9. A process for producing a compound represented by formula [VIIa]: 
wherein R2 and A are as defined in the above item 5, and R5 and R6 are as defined in the above item 7, or a salt thereof, which comprises reacting a compound represented by formula [Va]: 
wherein R5 and R6 are as defined in the above item 7, or a salt thereof with a compound represented by formula [VI]: 
wherein R2 and A are as defined in the above item 5, or a salt thereof;
10. A process for producing a compound represented by formula [IXa]: 
wherein R2 and A are as defined in the above item 5, R4 and n are as defined in the above item 6, and R5 and R6 are as defined in the above item 7, or a salt thereof, which comprises reacting a compound represented by formula [VIIa]: 
wherein R2 and A are as defined in the above item 5, and R5 and R6 are as defined in the above item 7, or a salt thereof with a compound represented by formula [VIII]:
R4SOnX2xe2x80x83xe2x80x83[VIII]
wherein R4, n and X2 are as defined in the above item 6;
11. 3-(5-Isoxazolyl)-xcex942-1,2,4-oxadiazoline represented by formula [II]: 
or a salt thereof;
12. A compound represented by formula [IV]: 
wherein R1 is as defined in the above item 3, or a salt thereof;
13. A compound represented by formula [V]: 
wherein R1 is as defined in the above item 3, or a salt thereof;
14. A compound represented by formula [VII]: 
wherein R1 is as defined in the above item 3, and R2 and A are as defined in the above item 5, or a salt thereof;
15. A compound represented by formula [IVa]: 
wherein X is as defined in the above item 7, or a salt thereof;
16. A compound represented by formula [IVb]: 
wherein R5 and R6 are as defined in the above item 7, or a salt thereof;
17. A compound represented by formula [Va]: 
wherein R5 and R6 are as defined in the above item 7, or a salt thereof; and
18. A compound represented by formula [VIIa]: 
wherein R2 and A are as defined in the above item 5, and R5 and R6 are as defined in the above item 7, or a salt thereof.
In the formulae above, the alkyl group in the optionally substituted alkyl group represented by R1 includes e.g. C1-6 alkyl groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl.
The substituent on the alkyl group include hydroxyl group, amino group, mono- or di-C1-6 alkylamino group (e.g., methylamino, ethylamino, propylamino, dimethylamino, diethylamino and the like), C1-6 alkoxy group (e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy and the like), C1-6 alkylthio group (e.g., methylthio, ethylthio, n-propylthio, isopropylthio, butylthio and the like), halogen atom (e.g., fluorine, chlorine, bromine, iodine), carboxyl group, nitro group, cyano group and the like. The substituent is particularly preferably a C1-6 alkoxy group.
The number of substituent is 1 to 6, preferably 1 to 3, within the replaceable range.
The acyl group in the optionally substituted acyl group represented by R1 includes C1-20 acyl groups derived from carboxylic acids, and examples thereof include (1) formyl, (2) alkanoyl group, preferably C2-10 alkanoyl group (e.g., C1-9 alkyl-carbonyl group such as acetyl, propionyl, butyryl, isobutyryl, pentanoyl, hexanoyl, heptanoyl, pivaloyl and the like), (3) cycloalkanoyl group, preferably C4-10 cycloalkanoyl group (e.g., cyclopropyl carbonyl, cyclobutyl carbonyl, cyclopentyl carbonyl, cyclohexyl carbonyl and the like), (4) alkenyl carbonyl group, preferably C3-10 alkenyl carbonyl group (e.g., acryloyl, allyl carbonyl, isopropenyl carbonyl, isobutenyl carbonyl, 1-methyl allyl carbonyl, cinnamoyl and the like), (5) alkynyl carbonyl group, preferably C3-7 alkynyl carbonyl group (e.g., propargyl carbonyl, 2-butynyl carbonyl, 3-butynyl carbonyl, 3-pentynyl carbonyl and the like), (6) aryl carbonyl group, preferably C7-14 aryl-carbonyl group (e.g., benzoyl, 1-naphthoyl, 2-naphthoyl and the like), (7) alkoxy carbonyl group, preferably C2-6 alkoxy-carbonyl group (e.g., methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl, tert-butoxycarbonyl and the like), (8) aryloxy carbonyl group, preferably C7-14 aryloxy-carbonyl group (e.g., phenoxy carbonyl group), (9) aralkyl carbonyl group, preferably C8-19 aralkyl-carbonyl group (e.g., phenyl-C1-4 alkyl carbonyl such as benzyl carbonyl, phenetyl carbonyl and phenyl propyl carbonyl, and naphthyl-C1-4 alkyl carbonyl such as benzhydryl carbonyl and 1-naphthyl ethyl carbonyl), (10) aralkyloxy carbonyl group, preferably C8-19 aralkyloxy carbonyl group (e.g., phenyl-C1-4 alkyloxy carbonyl such as benzyloxy carbonyl, phenetyloxy carbonyl and phenyl propyloxy carbonyl), (11) carbamoyl group, and (12) cyclic aminocarbonyl group (e.g., 1-pyrrolidinocarbonyl, piperidinocarbonyl, morpholinocarbonyl, thiomorpholinocarbonyl and 1-perhydroazepinyl carbonyl and the like).
When the acyl group is an alkanoyl group, alkenyl carbonyl group or alkynyl carbonyl group, the group may have 1 to 6 (preferably 1 to 3) substituents such as hydroxyl group, amino group, mono- or di-C1-6 alkylamino group (e.g., methylamino, ethylamino, propylamino, dimethylamino, diethylamino and the like), C1-6 alkoxy group (e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy and the like), C1-6 alkylthio group (e.g., methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio and the like), halogen atom (e.g., fluorine, chlorine, bromine, iodine), carboxyl group, nitro group, cyano group, phenyl group and the like.
When the acyl group is cycloalkanoyl group, aryl carbonyl group, alkoxycarbonyl group, aryloxy carbonyl group, aralkyl carbonyl group or aralkyloxy carbonyl group, the group may have 1 to 5 (preferably 1 to 3) substituents such as hydroxyl group, amino group, mono- or di-C1-6 alkylamino group (e.g., methylamino, ethylamino, propylamino, dimethylamino, diethylamino and the like), C1-6 alkoxy group (e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy and the like), C1-6 alkylthio group (e.g., methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio and the like), halogen atom (e.g., fluorine, chlorine, bromine, iodine), carboxyl group, nitro group, cyano group, phenyl group, C1-6 alkyl group (e.g., methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl and the like), C2-6 alkenyl group (e.g., vinyl, allyl, 1-propenyl, 1-butenyl, 2-butenyl and the like), C2-6 alkynyl group (e.g., ethynyl, 1-propynyl, propargyl, 1-butynyl and the like) and the like
When the acyl group is a carbamoyl group, the group may have 1 or 2 substituents such as (1) C1-6 alkyl group (e.g., methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl and the like), (2) C3-9 cycloalkyl group (e.g., cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and the like), (3) C2-6 alkenyl group (e.g., vinyl, allyl, 1-propenyl, 1-butenyl, 2-butenyl and the like), (4) C2-6 alkynyl group (e.g., ethynyl, 1-propynyl, propargyl, 1-butynyl and the like), (5) hydroxyl group, (6) C1-6 alkoxy group (e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy and the like), (7) amino group, (8) mono- or di-C1-6 alkyl amino group (e.g., methylamino, ethylamino, propylamino, dimethylamino, diethylamino and the like), (9) cyclic amino group (e.g., 1-pyrrolidino, piperidino, morpholino, 4-methyl-1-piperazino and the like) or (10) phenyl group, and the substituent, together with the nitrogen atom to which it is bonded, may form a cyclic amino group (e.g., 1-pyrrolidino, piperidino, morpholino, thiomorpholino, 4-methyl-1-piperazino and the like). Further, the substituent may be substituted with 1 to 6 (preferably 1 to 3) substituents selected from hydroxyl group, amino group, mono- or di-C1-6 alkylamino group (e.g., methylamino, ethylamino, propylamino, dimethylamino, diethylamino and the like), C1-6 alkoxy group (e.g., methoxy, ethoxy, propoxy, isopropoxy, butoxy and the like), C1-6 alkylthio group (e.g., methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio and the like), halogen atom (e.g., fluorine, chlorine, bromine, iodine), phenyl group, carboxyl group, nitro group and cyano group.
R1 is, out of those groups described above, preferably an optionally substituted alkyl group, an optionally substituted alkanoyl group, an optionally substituted cycloalkanoyl group, an optionally substituted alkenyl carbonyl group, an optionally substituted aryl carbonyl group, an optionally substituted alkoxy carbonyl group or an optionally substituted carbamoyl group, more preferably an optionally substituted carbamoyl group. R1 is particularly preferably (1) a C1-6 alkyl group optionally substituted with one to three C1-6 alkoxy, (2) a C2-10 alkanoyl group optionally substituted with one to three amino being optionally substituted with one or two C1-6 alkyl groups, C1-6 alkoxy, phenyl or halogen, (3) a C4-10 cycloalkanoyl group, (4) a C3-10 alkenyl carbonyl group, (5) benzoyl group, (6) carbamoyl group optionally substituted with one or two C1-6 alkyl, C3-9 cycloalkyl, C2-6 alkenyl, C2-6 alkynyl, phenyl, amino optionally substituted with one or two C1-6 alkyl, cyclic amino (for example, pyrrolidino, piperidino), hydroxyl or C1-6 alkoxy, which may be substituted with one to three substituents selected from amino optionally substituted with one or two C1-6 alkyl, phenyl, halogen and C1-6 alkyl, (7) a cyclic amino-carbonyl group (for example, pyrrolidinocarbonyl, piperidinocarbonyl, 1-perhydroazepinyl carbonyl, 4-methyl-1-piperazinyl carbonyl, morpholinocarbonyl), (8) a C2-6 alkoxy-carbonyl group optionally substituted with one to three halogen atoms, (9) a C7-14 aryloxy carbonyl group or (10) a formyl group. More preferable groups represented by R1 include a di-C1-6 alkyl carbamoyl group, morpholinocarbonyl group, 1-chloroethoxy carbonyl group, chloromethoxy carbonyl group, phenoxy carbonyl group and the like.
The halogen atom in X1 and R2 includes fluorine, chlorine, bromine and iodine. Particularly, chlorine is preferable.
The C1-6 haloalkyl group represented by R2 includes e.g. a C1-6 alkyl group substituted with one to ten (preferably one to five) halogens (for example, fluorine, chlorine, bromine, iodine), such as chloromethyl, fluoromethyl, bromomethyl, 2-chloroethyl, dichloromethyl, trichloromethyl, trifluoromethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, heptafluoropropyl, nonafluorobutyl and the like. Particularly, trifluoromethyl is preferable.
The C1-6 haloalkoxy group represented by R2 includes e.g. a C1-6 alkoxy group substituted with one to ten (preferably one to five) halogens (for example, fluorine, chlorine, bromine, iodine), such as chloromethoxy, fluoromethoxy, bromomethoxy, 2-chloroethoxy, dichloroethoxy, trichloromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, pentafluoroethoxy, heptafluoropropoxy and nonafluorobutoxy. Particularly, trifluoromethoxy is preferable.
The C1-6 haloalkyl group in the xe2x80x9cphenyl group optionally substituted with a C1-6 haloalkyl groupxe2x80x9d represented by R2 includes the C1-6 haloalkyl groups described above. The number of substituents on the phenyl group is 1 to 5, preferably 1 to 3. In particular, a phenyl group optionally substituted with one to three trifluoromethyl groups is preferable.
In particular, A is preferably 
The C1-6 alkyl group represented by R4 includes the C1-6 alkyl groups exemplified above for R1.
The C1-6 haloalkyl group represented by R4 includes the C1-6 haloalkyl groups exemplified above for R2. In particular, trifluoromethyl is preferable.
The halogen atom represented by X2 includes fluorine, chlorine, bromine and iodine. In particular, chlorine is preferable.
The C1-6 alkyl group represented by R5 and R6 includes the C1-6 alkyl groups exemplified above for R1. In particular, methyl is preferable.
The cyclic amino group formed by R5 and R6 together with their adjacent nitrogen atom includes e.g. cyclic amino groups such as 1-pyrrolidino, piperidino, morpholino and 4-methyl-1-piperazino. In particular, morpholino is preferable.
The reaction schemes in the present invention are as follows. 
In the reaction scheme 1, 5-cyanoisoxazole is reacted with hydroxylamine or a salt thereof, whereby isoxazole-5-carboxamide oxime represented by compound [I] or a salt thereof can be produced.
The salt of compound [I] usually includes salts with acids, and the acids include e.g. inorganic protonic acids such as hydrochloric acid, hydrobromic acid, hydriodic acid, phosphoric acid and sulfuric acid, organic protonic acids such as formic acid, acetic acid, tartaric acid, malic acid, citric acid, oxalic acid, succinic acid, benzoic acid, trifluoroacetic acid and p-toluene sulfonic acid, and Lewis acids such as aluminum chloride, ferric chloride, zinc chloride, titanium tetrachloride and boron trifluoride.
5-Cyanoisoxazole used as the starting material is a known compound (Gazz. chim. ital. 62, 436 (1932), bp. 168xc2x0 C.). This starting compound can be isolated for use, but it can also be generated by dehydration reaction of its precursor 5-isoxazole carboxamide, and subjected directly or after isolation to the subsequent reaction. 
The dehydrating agent in the reaction scheme includes known dehydrating agents such as phosphorus pentaoxide, phosphorus pentachloride, phosphorus oxychloride, thionyl chloride, trifluoroacetic anhydride, phosgene and dicyclohexyl carbodiimide. The dehydrating reaction can be conducted by a method described in e.g. xe2x80x9cOrganic Functional Group Preparations Second Editionxe2x80x9d Academic Press, Vol. 1, Chapter 17 (1983) or by an analogous method.
Compound [I] occurs as geometrical isomers described below, and the present invention encompasses all the isomers and mixtures thereof. 
Hydroxylamine used in this reaction or a salt thereof can be used in any form, and for example, it can be subjected to the reaction in the form of hydrochloride, sulfate or an aqueous solution.
In this reaction, the amount of hydroxylamine or a salt thereof is not particularly limited, and hydroxylamine or a salt thereof also serving as a solvent can be used in large excess, preferably in an amount of about 0.8 to 5 equivalents.
For the purpose of promoting the reaction or decreasing byproducts, a base is coexistent or allowed to act before and after the reaction, whereby good results may be obtained. The base includes e.g. alkali metal alcoholates such as sodium ethylate, sodium methylate and potassium tert-butoxide, organic bases such as ammonia, triethylamine, diisopropyl ethylamine, pyridine, 4-dimethyl aminopyridine and N,N-dimethyl aniline, and inorganic bases such as potassium carbonate, sodium carbonate, sodium hydroxide, potassium hydroxide, sodium bicarbonate, potassium bicarbonate and sodium hydride. The amount of the base used is not particularly limited insofar as the reaction is not adversely affected, and the base also serving as a solvent can be used in large excess.
This reaction can be carried out in a suitable solvent. The solvent is not particularly limited unless it reacts with the reaction substrate, the reaction reagent and the product to give byproducts, and the solvent is desirably the one dissolving both the reaction substrate and the reaction reagent. Such solvent includes e.g. aliphatic hydrocarbons such as pentane, hexane, heptane and petroleum ether, aromatic hydrocarbons such as benzene, toluene and xylene, esters such as methyl acetate, ethyl acetate, ethyl formate and ethyl propionate, alcohols such as methanol, ethanol, propanol, isopropanol and butanol, ketones such as acetone and methyl ethyl ketone, ethers such as diethyl ether, dipropyl ether, diisopropyl ether, dibutyl ether, tetrahydrofuran and dioxane, nitriles such as acetonitrile and propionitrile, acid amides such as dimethyl formamide and dimethyl acetamide, sulfoxides such as dimethyl sulfoxide, sulfones such as sulfolane, phosphoric acid amides such as hexamethyl phosphoramide, halogenated hydrocarbons such as dichloromethane, chloroform, 1,2-dichloroethane and carbon tetrachloride, and aromatic amines such as pyridine, picoline, lutidine and quinoline, as well as mixed solvents thereof, water, and mixed solvents thereof with water.
The reaction temperature is usually xe2x88x9230 to 150xc2x0 C., preferably xe2x88x9210 to 80xc2x0 C. The reaction time is usually 0.1 to 72 hours, more preferably about 0.1 to 24 hours.
The resultant compound [I] or a salt thereof can be subjected as the starting material in the subsequent reaction in the form of the reaction mixture or after separation and purification by a means known per se, for example, concentration, concentration under reduced pressure, conversion of liquid properties, transfer to other solvent, solvent extraction, distillation, crystallization, recrystallization and chromatography.
In the reaction formula 1, isoxazole-5-carboxamide oxime represented by compound [I] or a salt thereof is reacted with formaldehyde or an equivalent thereof, whereby 3-(5-isoxazolyl)-xcex942-1,2,4-oxadiazoline represented by compound [II] or a salt thereof can be produced.
The salt of compound [II] includes salts with the acids exemplified above in compound [I].
Usually, compound [II] occurs as tautomers described below, and the present invention encompasses all such tautomers and mixtures thereof. 
Formaldehyde used in the present invention or an equivalent thereof includes formaldehyde, formalin (aqueous solution of formaldehyde), para-formaldehyde and dimethoxymethane. The amount thereof is not particularly limited, and also serving as a solvent, it can also be used in large amount, preferably in an amount of 0.8 to 15 equivalents.
For the purpose of promoting the reaction or decreasing byproducts, an acid is coexistent or allowed to act before and after the reaction, whereby good results may be obtained. Such acid catalysts include e.g. inorganic protonic acids such as hydrochloric acid, hydrobromic acid, hydriodic acid, phosphoric acid and sulfuric acid, organic protonic acids such as formic acid, acetic acid, tartaric acid, malic acid, citric acid, oxalic acid, succinic acid, benzoic acid, trifluoacetic acid and p-toluene sulfonic acid, and Lewis acids such as aluminum chloride, ferric chloride, zinc chloride, titanium tetrachloride and boron trifluoride. The amount of the acid catalyst used in the reaction is not particularly limited insofar as the reaction is not adversely affected, and the acid catalyst also serving as a solvent can be used in large excess. The acid is particularly preferably acetic acid or p-toluene sulfonic acid.
This reaction can be carried out in a suitable solvent. The solvent is not particularly limited unless it reacts with the reaction substrate, the reaction reagent and the product to give byproducts, and the solvent is desirably the one dissolving both the reaction substrate and the reaction reagent, and for example, the solvent described above in producing compound [I] is similarly used.
The reaction temperature is usually xe2x88x9230 to 200xc2x0 C., preferably 0 to 150xc2x0 C. The reaction time is generally 0.1 to 96 hours, more preferably about 0.1 to 48 hours.
The resultant compound [II] or a salt thereof can be subjected as the starting material in the subsequent reaction in the form of the reaction mixture or after separation and purification by a means known per se, for example, concentration, concentration under reduced pressure, conversion of liquid properties, transfer to other solvent, solvent extraction, distillation, is crystallization, recrystallization and chromatography.
In the reaction scheme 1, 3-(5-isoxazolyl)-xcex942-1,2,4-oxadiazoline represented by compound [II] or a salt thereof is reacted with compound [III], whereby compound [IV] or a salt thereof can be produced.
The salt of compound [IV] includes salts with the acids exemplified above for compound [I].
Compound [III] or an equivalent thereof includes e.g. phosgene, trichloromethyl chloroformate (diphosgene), bistrichloromethyl carbonate (triphosgene), 1-chloroethyl chloroformate, and an acylating agent represented by R1COL [R1 has the same meaning as defined above, and L represents a halogen atom (for example, fluorine, chlorine, bromine, iodine), acyloxy group (C1-10 acyloxy group, for example, formyloxy group; C1-6 alkyl-carbonyloxy group optionally substituted with 1 to 3 halogen atoms, such as acetoxy group, propionyloxy group and trifluoroacetoxy group; and C1-6 alkoxy-carbonyloxy group such as methoxycarbonyloxy and t-butoxycarbonyloxy]. Compound [III] is a known compound or can be produced easily from a known compound.
Compound [III] used in this reaction or an equivalent thereof may have formed a salt. Such salts include e.g. salts with inorganic protonic acids such as hydrochloric acid, hydrobromic acid, hydriodic acid, phosphoric acid and sulfuric acid, salts with organic protonic acids such as formic acid, acetic acid, tartaric acid, malic acid, citric acid, oxalic acid, succinic acid, benzoic acid, trifluoacetic acid and p-toluene sulfonic acid, and salts with Lewis acids such as aluminum chloride, ferric chloride, zinc chloride, titanium tetrachloride and boron trifluoride.
The amount of compound [III] used in this reaction or an equivalent thereof is not particularly limited insofar as the reaction is adversely affected, and the amount thereof is preferably 0.8 to 5 equivalents.
For the purpose of promoting the reaction with decreasing byproducts, a base is coexistent or allowed to act before and after the reaction, whereby good results may be obtained. As the base, the base described above in producing compound [I] is similarly used. The amount of the base used is not particularly limited insofar as the reaction is not adversely affected, and the base also serving as a solvent can be used in large excess.
This reaction can be carried out in a suitable solvent. The solvent is not particularly limited unless it reacts with the reaction substrate, the reaction reagent and the product to give byproducts, and the solvent is desirably the one dissolving both the reaction substrate and the reaction reagent, and for example, the solvent described above in producing compound [I] is similarly used.
The reaction temperature is usually about xe2x88x9250 to 200xc2x0 C., more preferably xe2x88x9230 to 150xc2x0 C. The reaction time is generally 0.1 to 96 hours, more preferably about 0.1 to 48 hours.
The resultant compound [IV] or a salt thereof can be subjected as the starting material in the subsequent reaction in the form of the reaction mixture or after separation and purification by a means known per se, for example, concentration, concentration under reduced pressure, conversion of liquid properties, transfer to other solvent, solvent extraction, distillation, crystallization, recrystallization and chromatography.
In the reaction scheme 1, the compound [IV] or a salt thereof can be subjected if necessary to the ring-opening reaction of the isoxazole ring, to produce compound [V] or a salt thereof. The salt of compound [V] includes salts with the acids exemplified above for compound [I].
Usually, compound [V] has tautomers described below, and the present invention encompasses all such tautomers and mixtures thereof. 
As the base used in this reaction, for example, the base described above in producing compound [I] is similarly used. The amount of the base is not particularly limited insofar as the reaction is not adversely affected, and the base also serving as a solvent can be used in large excess, preferably in an amount of 0.8 to 5 equivalents.
This reaction can be carried out using a suitable solvent. Such solvent is not particularly limited unless it reacts with the reaction substrate, the reaction reagent and the product to give byproducts, and the solvent is desirably the one dissolving the reaction substrate and the reaction reagent, and for example, the solvent enumerated above in production of compound [I] is similarly used.
The reaction temperature is usually xe2x88x9250 to 200xc2x0 C., preferably xe2x88x9230 to 150xc2x0 C. The reaction time is usually 0.1 to 96 hours, more preferably about 0.1 to 48 hours.
The resultant compound [V] or a salt thereof can be subjected as the starting material in the subsequent reaction in the form of the reaction mixture or after separation and purification by a means known per se, for example, concentration, concentration under reduced pressure, conversion of liquid properties, transfer to other solvent, solvent extraction, distillation, crystallization, recrystallization and chromatography.
In the reaction scheme 1, compound [V] or a salt thereof is reacted with a hydrazine derivative represented by compound [VI] or a salt thereof, whereby compound [VII] or a salt thereof can be synthesized. The salts of compounds [VI] and [VII] include the acids exemplified above for compound [I]. Compound [VI] is, for example, 2,6-dichloro-4-trifluoromethyl phenyl hydrazine, and it is a known compound or can be produced easily from a known compound. This reaction proceeds via hydrazone derivative [XI] as intermediate as shown in the reaction scheme below, and the intermediate [XI] can also be generally isolated. Subsequently, a base is allowed to act on [XI] formed as intermediate, thus converting it into compound [VII] or a salt thereof. 
In the reaction of compound [V] or a salt thereof with compound [VI], the reaction may be promoted in the presence of a suitable acid catalyst if necessary. As the acid catalyst, the acid described above in producing compound [II] is similarly used. The amount of the acid used is not particularly limited insofar as the reaction is not adversely affected, and the acid also serving as a solvent can be used in large excess.
As the base used in conversion of the intermediate [XI] thorough ring closure into compound [VII] or a salt thereof, the base described above in producing compound [I] is similarly used. The amount of the base used is not particularly limited insofar as the reaction is adversely affected, and the base also serving as a solvent can be used in large excess, preferably in an amount of 0.8 to 5 equivalents.
When the reaction of converting the compound [IV] into compound [V] is followed by this reaction, good results may be obtained.
This reaction can be carried out in a suitable solvent. The solvent is not particularly limited unless it reacts with the reaction substrate, the reaction reagent and the product to give byproducts, and the solvent is desirably the one dissolving both the reaction substrate and the reaction reagent, and for example, the solvent described above in producing compound [I] is similarly used.
The reaction temperature is usually xe2x88x9250 to 200xc2x0 C., preferably xe2x88x9230 to 150xc2x0 C. The reaction time is usually 0.1 to 96 hours, more preferably about 0.1 to 48 hours.
The resultant compound [VII] or a salt thereof can be subjected as the starting material in the subsequent reaction in the form of the reaction mixture or after separation and purification by a means known per se, for example, concentration, concentration under reduced pressure, conversion of liquid properties, transfer to other solvent, solvent extraction, distillation, crystallization, recrystallization and chromatography.
In the reaction scheme 1, the compound [VII] or a salt thereof can be reacted with compound [VIII] to produce compound [IX] or a salt thereof. The salt of compound [IX] includes salts with the acids exemplified above for compound [I]. The compound [VIII] is, for example, trifluoromethane sulphenyl chloride or trifluoromethane sulfinyl chloride, and it is a known compound or can be easily produced from a known compound.
The amount of compound [VIII] used in this reaction is not particularly limited, and is preferably about 0.8 to 5 equivalents.
For the purpose of promoting the reaction while lessening byproducts, an organic base salt is coexistent, whereby good results may be obtained. The organic base salt includes e.g. dimethylamine hydrochloride, dimethylamine-p-toluene sulfonate, triethylamine hydrochloride, pyridine hydrochloride, and pyridine-p-toluene sulfonate. Further, a suitable acid or base catalyst is allowed to coexist, whereby good results may be obtained. As the acid or base catalyst, the base described above in producing compound [I] or the acid described above in producing compound [II] is used. The amount of the organic base salt, acid and base used as the catalyst is not particularly limited insofar as the reaction is not adversely affected, and such salt, acid and base also serving as a solvent can be used in large excess, preferably in an amount of 0.8 to 5 equivalents.
This reaction can be carried out in a suitable solvent. The solvent is not particularly limited unless it reacts with the reaction substrate, the reaction reagent and the product to give byproducts, and the solvent is desirably the one dissolving both the reaction substrate and the reaction reagent, and for example, the solvent described above in producing compound [I] is similarly used.
The reaction temperature is usually about xe2x88x9250 to 200xc2x0 C., preferably xe2x88x9230 to 150xc2x0 C. The reaction time is generally 0.1 to 96 hours, more preferably about 0.1 to 48 hours.
The resultant compound [IX] or a salt thereof can be subjected as the starting material in the subsequent reaction in the form of the reaction mixture or after separation and purification by a means known per se, for example, concentration, concentration under reduced pressure, conversion of liquid properties, transfer to other solvent, solvent extraction, distillation, crystallization, recrystallization and chromatography.
The reaction scheme 2, when compound [IV] in the reaction scheme 1 represents compound [IVa], shows the reaction of producing compounds [Va], [VIIa] and [IXa] (included in compounds [V], [VII] and [IX], respectively) via compound [IVb], and the reaction scheme 2 is included in the reaction scheme 1.
In the reaction scheme 2, compound [II] or a salt thereof is reacted with phosgene or an equivalent thereof or 1-chloroethyl chlorocarbonate, whereby compound [IVa] or a salt thereof can be produced. Compound [IVa] or a salt thereof can be generally isolated, but when compound [IVa] is instable as in reaction with phosgene or an equivalent thereof (when X=Cl), compound [IVa] is subjected desirably without isolation to the subsequent reaction. The salt of compound [IVa] includes the salts described above for compound [IV].
As the phosgene used in this reaction or an equivalent thereof, phosgene, trichloromethyl chloroformate (diphosgene), bistrichloromethyl carbonate (triphosgene) etc are used. The amount thereof is not particularly limited, and is preferably 0.3 to 5 equivalents.
For the purpose of promoting the reaction with decreasing byproducts, a base is coexistent or allowed to act before and after the reaction, whereby good results may be obtained. As the base, the base described above in producing compound [I] is similarly used. The amount of the base used is not particularly limited insofar as the reaction is not adversely affected, and is preferably 0.3 to 5 equivalents.
This reaction can be carried out in a suitable solvent. The solvent is not particularly limited unless it reacts with the reaction substrate, the reaction reagent and the product to give byproducts, and the solvent is desirably the one dissolving both the reaction substrate and the reaction reagent, and for example, the solvent described above in producing compound [I] is similarly used.
The reaction temperature is usually about xe2x88x9250 to 200xc2x0 C., preferably xe2x88x9230 to 150xc2x0 C. The reaction time is generally 0.1 to 96 hours, more preferably about 0.1 to 48 hours.
The resultant compound [IVa] or a salt thereof can be subjected as the starting material in the subsequent reaction in the form of the reaction mixture or after separation and purification by a means known per se, for example, concentration, concentration under reduced pressure, conversion of liquid properties, transfer to other solvent, solvent extraction, distillation, crystallization, recrystallization and chromatography.
In the reaction scheme 2, compound [IVa] or a salt thereof is reacted with an amine represented by R5R6NH, whereby compound [IVb] or a salt thereof can be produced.
The amine represented by R5R6NH is a known compound such as dimethylamine, diethylamine, di-n-propylamine, dibutylamine, di-n-butylamine, methyl ethylamine, ethyl n-propylamine, pyrrolidine, piperidine, morpholine or N-methyl piperazine, or can be easily produced from the known compound.
The amount of the amine used in this reaction is not particularly limited, and is preferably about 0.8 to 5 equivalents.
This reaction can be carried out in a suitable solvent. The solvent is not particularly limited unless it reacts with the reaction substrate, the reaction reagent and the product to give byproducts, and the solvent is desirably the one dissolving both the reaction substrate and the reaction reagent, and for example, the solvent described above in producing compound [I] is similarly used.
The reaction temperature is usually about xe2x88x9250 to 200xc2x0 C., preferably xe2x88x9230 to 150xc2x0 C. The reaction time is generally 0.1 to 72 hours, more preferably about 0.1 to 24 hours.
The resultant compound [Vbb] or a salt thereof can be subjected as the starting material in the subsequent reaction in the form of the reaction mixture or after separation and purification by a means known per se, for example, concentration, concentration under reduced pressure, conversion of liquid properties, transfer to other solvent, solvent extraction, distillation, crystallization, recrystallization and chromatography.
The process of conversion of compound [IVb]xe2x86x92[Va]xe2x86x92[VIIa]xe2x86x92[IXa] in the reaction scheme 2 can be carried out in accordance with the process of conversion of compound [IV]xe2x86x92[V]xe2x86x92[VII]xe2x86x92[IX] in the reaction scheme 1.
The compounds [IX] and [IXa] and salts thereof produced according to the process of the present invention are effective for control of hygienically harmful insects, animal and plant parasitic insects, and exhibit strong insecticidal action by application to animal and plants where the parasitic insects live. The chemical damage to plants by the compound [I] of the present invention and a salt thereof is low, and the toxicity thereof on fishes is also low, so that they have safety and advantageous properties as agents for controlling harmful insects in medical goods, livestock industry, pets, horticulture, and agriculture (Japanese Patent Application No. 11-151959).
For use of the compounds [IX] and [IXa] or salts thereof as agrochemicals particularly as insecticides, one or more (preferably one to three) of compounds [IX] and [IXa] or salts thereof as active ingredients are dissolved or suspended in suitable liquid carriers, or mixed with, or absorbed onto, suitable solid carriers depending on the intended use in the form of agrochemical, pharmaceutical or veterinary preparations such as emulsifiable concentrates, liquid preparation, micro-emulsion, flowable concentrates, oil solution, wettable powders, dusts, granules, fine granules, seed-coating, smoking pesticides, tablets, microcapsules, sprays, EW, ointments, and poisonous bait. These agrochemical, pharmaceutical or veterinary preparations can be prepared in a method known per se by adding e.g. an emulsifier, a suspending agent, a spreading agent, a penetrant, a wetting agent, a thickening agent and a stabilizer, if necessary.
The liquid carriers (solvents) used are preferably solvents such as water, alcohols (for example, methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, ethylene glycol and the like), ketones (for example, acetone, methyl ethyl ketone and the like), ethers (for example, dioxane, tetrahydrofuran, ethylene glycol monomethyl ether, diethylene glycol monomethyl ether, propylene glycol monomethyl ether and the like), aliphatic hydrocarbons (for example, kerosine, kerosene, fuel oil, machine oil and the like), aromatic hydrocarbons (for example, benzene, toluene, xylene, solvent naphtha, methyl naphthalene and the like), halogenated hydrocarbons (for example, dichloromethane, chloroform, carbon tetrachloride and the like), acid amides (for example, N,N-dimethylformamide, N,N-dimethyl acetamide and the like), esters (for example, ethyl acetate, butyl acetate, fatty acid glycerine ester and the like), nitriles (for example, acetonitrile, propionitrile and the like), and these can be used alone or in combination thereof (preferably one to three solvents) in a suitable ratio.
As the solid carriers (diluents and fillers), use is made of plant powders (for example, soybean powder, tobacco powder, wheat flour, wood meal and the like), mineral powders (for example, clays such as kaolin, bentonite and acid clay, talc such as talcum powder and pagodite powder, silica such as diatomaceous earth and mica powder, and the like), alumina, sulfur powder, activated carbon and the like, and one or more (preferably one to three) of these carriers can be mixed in a suitable ratio before use.
Examples of ointment bases suitably added include polyethylene glycol and pectin, higher fatty acid-polyvalent alcohol esters such as monostearic acid glycerine ester, cellulose derivatives such as methyl cellulose, sodium alginate, bentonite, higher alcohols, polyvalent alcohols such as glycerine, vaseline, white vaseline, liquid paraffin, lard, various vegetable oils, lanoline, dehydrated lanoline, hardened oil and one or more (preferably one to three) resins, to which the following surfactants may be added, if necessary.
The surfactants suitably used as an emulsifier, wetting agent, penetrant, dispersant and the like are nonionic and anionic surfactants such as soaps, polyoxyethylene alkyl aryl ethers [for example, Noigen (trade name), E.A142 (trade name) produced by Dai-ichi Kogyo Seiyaku Co., Ltd., and Nonal (trade name) produced by Toho Chemical Co., Ltd.], alkyl sulfates [for example, Emal 10 (trade name), Emal 40 (trade name) produced by Kao Corporation], alkyl sulfonates [for example, Neogen (trade name), Neogen T (trade name) produced by Dai-ichi Kogyo Seiyaku Co., Ltd., and Neopelex produced by Kao Corporation], polyethylene glycol ethers [for example, Nonipol 85 (trade name), Nonipol 100 (trade name), Nonipol 160 (trade name) produced by Sanyo Chemical Industries, Ltd.], polyvalent alcohol esters [for example, Tween 20 (trade name), Tween 80 (trade name) produced by Kao Corporation]. Further, compound [I] or a salt thereof can be compounded suitably with other insecticides (pyrethroid insecticides, organo phosphorus insecticides, carbamate insecticides, neonicotinoide insecticides, naturally occurring insecticides and the like), acaricides, nematicides, herbicides, plant hormones, plant growth regulators, fungicides (for example, copper fungicide, organic chloride fungicide, organic sulfur fungicide, phenolic fungicide and the like), synergistic agents, attractants, repellents, pigments, fertilizers and the like
In the agrochemical composition (insecticide) comprising the compounds produced according to the process of the present invention, the content of compounds [IX] and [IXa] or salts thereof is usually about 0.1 to 80% by weight, preferably about 1 to 20% by weight, based on the total weight of the composition. Specifically, when these active ingredients are used in an emulsifier, liquid, wettable powder (for example, a granular wettable powder) and the like, the content thereof is usually about 1 to 80% by weight, preferably about 1 to 20% by weight. When these active ingredients are used in oil, powder and the like, the content thereof is usually about 0.1 to 50% by weight, preferably about 0.1 to 20% by weight. When the active ingredients are used in powder, the content thereof is usually about 5 to 50% by weight, preferably about 1 to 20% by weight.
The amount of other agricultural active ingredients (for example, insecticides, herbicides, acaricides and/or fungicides) incorporated into the agrochemical composition of the present invention is usually in the range of about 1 to 80% by weight, preferably about 1 to 20% by weight, based on the total weight.
The content of additives other than the active ingredients described above is varied depending on the type or content of the agrochemical active ingredients or the form of the formulation, but is usually about 0.001 to 99.9% by weight, preferably about 1 to 99% by weight. Specifically, a surfactant is added in an amount of usually about 1 to 20% by weight, preferably about 1 to 15% by weight, a fluidizing additive in an amount of about 1 to 20% by weight, a carrier in an amount of about 1 to 90% by weight, preferably about 1 to 70% by weight, based on the total weight of the composition. Specifically, when the liquid is produced, it is preferable to add a surfactant in an amount of usually about 1 to 20% by weight, preferably about 1 to 10% by weight and water in an amount of about 20 to 90% by weight. For use, an emulsifier, a hydrating agent (for example, a granular wettable powder) and the like may be sprayed after suitable dilution with e.g. water (for example, about 100- to 5,000-fold).
Typical examples of insecticides, acaricides and fungicides which can be used by mixing with compounds [IX] and [IXa] or salts thereof produced according to the process of the present invention are shown below:
EPN, acephate, isoxathion, isofenphos, isoprocarb, etrimfos, oxydeprofos, quinalphos, cadusafos, chlorethoxyfos, chlorpyrifos, chlorpyrifos-methyl, chlorofenvinphos, salithion, cyanophos, disulfoton, dimethoate, sulprofos, diazinon, thiometon, tetrachlorvinphos, tebupirimfos, trichlorphon, naled, vamidothion, pyraclophos, pyridafenthion, pirimiphos-methyl, fenitrothion, fenthion, phenthoate, fosthiazate, butathiofos, prothiofos, propaphos, profenofos, phosalone, fosthiazate, malathion, methidathion, metolcarb, monocrotophos, BPMC, XMC, alanycarb, ethiofencarb, carbaryl, carbosulfan, carbofuran, xylylcarb, cloethocarb, thiodicarb, triazamate, pirimicarb, fenoxycarb, fenothiocarb, furathiocarb, propoxur, bendiocarb, benfuracarb, methomyl, acrinathrin, imiprothrin, ethofenprox, cycloprothrin, sigma-cypermethrin, cyhalothrin, cyfluthrin, cypermethrin, silafluofen, tefluthrin, deltamethrin, tralomethrin, fenvalerate, fenpropathrin, flucythrinate, fluvalinate, flufenoprox, fluproxyfen, flumethrin, prallethrin, beta-cyfluthrin, benfluthrin, permethrin, acetamiprid, imidacloprid, cartap, thiocyclam, nitenpyram, clotianidine, tefuranidine, AKD-1022, thiomethoxam, bensultap, avermectin, emamectin-benzoate, clofentezine, chlorfluazuron, cyromazine, diafenthiuron, dienochlor, dichlorvos, diflubenzuron, spynosyn, sulfluramid, teflubenzuron, tebufenozide, tebufenpyrad, hydroprene, vaniliprole, pymetrozine, pyridaben, pyriproxyfen, pyrimidifen, fipronil, fenazaquin, fenpyroximate, fluazuron, flucycloxuron, flufenoxuron, buprofezin, hexaflumuron, hexythiazox, milbemycin, metoxadiazone, lufenuron, levamisol, chlorphenapyr, NC-184, etoxazole, IBP, ampropylfos, edifenphos, chlorthiophos, tolclofos-methyl, fosetyl, ipconazole, imazalil, imibenconazole, etaconazole, epoxiconazole, cyproconazole, diniconazole, difenoconazole, tetraconazole, tebuconazole, triadimenol, triadimefon, triticonazole, triforine, bitertanol, viniconazole, fenarimol, fenbuconazole, fluotrimazole, furconazole-cis, flusilazole, flutriafol, bromuconazole, propiconazole, hexaconazole, pefurazoate, penconazole, myclobutanil, metconazole, cabendazin, debacarb, prothiocarb, benomyl, maneb, TPN, isoprothiolane, iprodione, iminoctadine-albesil, iminoctadine-triacetate, ethirimol, etridiazole, oxadixyl, oxycarboxin, oxolinic acid, ofurace, kasugamycin, carboxin, captan, clozylacon, chlobenthiazone, cyprodinil, cyprofuram, diethofencarb, dichlofluanid, diclomezine, zineb, dimethirimol, dimethomorph, dimefluazole, thiabendazole, thiophanate-methyl, thifluzamide, tecloftalam, triazoxide, triclamide, tricyclazole, tridemorph, triflumizole, validamycin A, hymexazol, pyracarbolid, pyrazophos, pyrifenox, pyrimethanil, pyroquilon, ferimzone, fenpiclonil, fenpropidin, fenpropimorph, fthalide, furametpyr, furalaxyl, fluazinam, furcarbanil, fluquinconazole, fludioxonil, flusulfamide, flutolanil, butiobate, prochloraz, procymidone, probenazole, benalaxyl, benodanil, pencycuron, myclozolin, metalaxyl, metsulfovax, methfuroxam, mepanipyrim, mepronil, kresoxim-methyl, azoxystrobin, SSF-126, and carpropamid.
Agrochemical preparations comprising the compounds [IX] and [IXa] or salts thereof produced according to the process of the present invention are advantageous for controlling harmful insects, for example, Hemiptera harmful insects such as Eurydema rugosum, Scotinophara lurida, Riptortus clavatus, Stephanitis nashi, Laodelphax striatellus, Nilaparvata lugens, Nephotettix cincticeps, Unaspis yanonensis, Aphis glycines, Lipaphis erysimi, Brevicoryne brassicae, Aphis gossypii, Myzus persicae, Aulacorthum solani, Aphis spiraecola, Bemisia tabaci, Trialeurodes vaporariorum, Sogatella furcifera, Empoasca onukii, Pseudococus comstocki, Planococcus citri, Icerya purchasi, Plautia stali, Eysarcoris parvus and the like, Lepidoptera harmful insects such as Spodoptera litura, Plutella xylostella, Pieris rapae crucivora, Chilosupppressalis, Autographa nigrisigna, Helicoverpa assulta, Pseudaletia separata, Mamestra brassicae, Adoxophyes orana fasciata, Notarcha derogata, Cnaphalocrocis medinalis, Phthorimaea operculella, Chilopolychrysus, Typoryza incertulas, Spodoptera exigua, Agrotis segetum, Agrotisipsilon, Heliothisarmigera, Heliothisvirescens, Heliothis zea, Narangaaenescens, Ostrinia nubilalis, Ostrinia furnacalis, Parnara guttata, Adoxophyes sp., Caloptilia theivora, Phyllonorycter ringoneella, Carposina niponensis, Grapholita molesta and the like, Coleoptera harmful insects such as Epilachna vigintioctopunc tata, Aulacophorafemoralis, Phyllotreta striolata, Oulema oryzae, Echinocnemus squameus, Lissorhoptrus oryzophilus, Anthonomusgrandis, Callosobruchus chinensis, Sphenophorus venatus, Popillia japonica, Anomala cuprea, Diabrotica spp., Leptinotarsa decemlineata, Agriotes spp., Lasioderma serricorne, Anthrenusverbasci, Tribolium castaneum, Lyctusbrunneus, Anoplophora malasiaca, Tomicus piniperda and the like, Diptera harmful insects such as Musca domestica, Culex popiens pallens, Tabanus trigonus, Delia antiqua, Delia platura, Anophelessinensis, Agromyza oryzae, Hydrellia griseola, Chlorops oryzae, Dacuscucurbitae, Ceratitis capitata, Liriomyza trifolii and the like, Orthoptera harmful insects such as Locustamigratoria, Gryllotalpa africana, Oxya yezoensis, Oxya japonica and the like, Thysanoptera harmful insects such as Thripstabaci, Thrips parmi, Frankliniella occidentalis, Baliothrips biformis, Scirtothrips dorsalis and the like, Hymenoptera harmful insects such as Athalia rosae and the like, Blattariae harmful insects such as Blattella germanica, Periplaneta fuliginosa, Periplaneta japonica, Periplaneta americana and the like, acaroid harmful insects such as Tetranychus urticae, Panonychuscitri, Tetranychus kanzawai, Tetranychuscinnabarinus, Panonychus ulmi, Aculopspelekassi, Polyphagotarsonemus latus, Rhizoglyphus echinopus and the like, nematodes such as Aphelenchoides besseyi, Meloidogyneincognita, Pratylenchus penetrans, Nothotylenchus acris and the like, and termites such as Coptotermes formosanus, Reticulitermes speratus, Odontotermes formosanus, Cryptotermes domesticus and the like.
Further, pharmaceutical or veterinary preparations comprising the compounds [IX] and [IXa] or salts thereof produced according to the process of the present invention can be used for keeping public health by expelling arthropods or parasites living in the inside or outside of vertebrates such as humans, cattle, sheep, goats, pigs, chickens, dogs, cats and fishes in the field of treatment of diseases in domestic animals and in livestock industry. For example, the parasites include Ixodes spp., Boophilus spp. (for example, Boophilus microplus), Amblyomma spp., Hyalomma spp., Rhipicephalus spp. (for example, Rhipicephalus appendiculatus), Haemaphysalis spp., Dermacentor spp., Ornithodoros spp. (for example, Ornithodoros moubata), Dermahyssus gallinae, Sarcoptes spp. (for example, Sarcoptes scabiei), Psoroptes spp., Chorioptes spp., Demodex spp., Eutrombicula spp., Aedes spp., Anopheles spp., Musca spp., Hypoderma spp., Gasterophilus spp., Simulium spp., Triatoma spp., Phthiraptera (for example, Damalinia spp., Linognathus spp.), Ctenocephalides spp., Monomorium pharaonis, and nematodes [for example trichostrongyles (for example, Nippostrongylus brasiliensis, Trichostrongylus axei, Trichostrongylus colubriformis), trichinae (for example, Trichinella spiralis), Haemonchus contortus, Nematodirus (for example, Nematodirus battus), Ostertagia circumcincta, Cooperia spp., Hymenolepis nana] and the like.
Agrochemical compositions comprising compounds [IX] and [IXa] or salts thereof produced according to the process of the present invention have excellent insecticidal activity and safety with very low toxicity, and can be used as excellent agrochemical compositions (insecticides). The agrochemical composition of the present invention can be used in the same manner as for conventional agrochemical compositions, and as a result, it can exhibit superior effects to those of the conventional compositions.
For example, the agrochemical composition of the present invention is sprayed in a method known per se into paddy fields, fields, orchards, non-agricultural fields, houses and the like, whereby it is contacted with, or ingested by, the above-described harmful insects growing therein to control them. In another mode, the agrochemical composition of the present invention is administered for example into the inside (into the body) or outside (onto the surface of the above-mentioned vertebrate), whereby arthropods or parasites living in the vertebrate can be expelled.
Specifically, the agrochemical composition of the present invention can be used against the intended harmful insects, for example, by seed treatment, nursery box treatment, planting hole treatment, planting foot treatment, soil treatment, foliar spraying, infusion, poisonous bait, smoking, drenching, or water application in paddy fields. The amount of the composition can be varied in a broad range depending on the application time, application site, application method and the like, but generally the active ingredients (compounds [IX] and [IXa] or salts thereof) are applied in an amount of about 0.3 to 3,000 g, preferably about 50 to 1,000 g, per hectare. Further, when the agrochemical composition is a wettable powder, it may be used after dilution such that the final concentration of the active ingredients is in the range of about 0.1 to 1,000 ppm, preferably about 10 to 500 ppm.